• 한국식품영양과학회지
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• 제27권1호
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• pp.141-148
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• 1998

This study describes the effects of 1,25-dihydroxyvitamin D3[1,25(OH)2D3, calcitriol] analog, 1,25(OH)2-16ene-23yne-D3 on proliferatin and differentiatin of the human histiocytic lymphoma cell line U937. This paper also describes the effects of 1,25(OH)2-16ene-23yne-D3 on ${\gamma}$-interferon(IFN-${\gamma}$) synthesis by phytohemagglutinin-activated peripheral blood lymphocytes(PBLs). In the present investigation, 1,25(OH2)-16ene-23yne-D3 was compared to the natural metablite of vitamin D3, 1,25(OH)2D3. 1,25(OH)2-16ene-23yne-D3 was more potent than 1,25(OH)2D3 for inhibition of proliferation and induction of differentiation of U937 cells, Its effects on inhibition of proliferation was about 30-fold more potent than 1,25(OH)2D3. On induction of differentiation as measured by nonspecific esterase (NSE) activity and morphologic change, this analog morphologically and functionally differentiated U937 cells to monocyte-macrophage phenotype showing a decrease of N/C ration in Giemsa staining and the increase of adherence ability of surface. After 3 days in culture, a more significant supression of IFN-${\gamma}$ synthesis analog on supression of IFN-${\gamma}$ synthesis was a dose-dependent manner, with peak activity at 10-7M. The strong direct effects of 1,25(OH)2-16ene-23yne-D3 on cell proliferation and cell differentiation, make this compound an interesting candidate for clinical studies for several types of malignancies, and the effects on supression of IFN-${\gamma}$ synthesis provide the further evidence for a role of 1,25(OH)2-16ene-23yne-D3 in immunoregulation.

• 대한치과교정학회지
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• 제25권3호
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• pp.333-339
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• 1995

[ $1,25-(OH)_2D_3$ ]가 치주인대세포의 증식에 미치는 영향과 조골세포 기능을 나타내는 지표이며 골의 석회화 과정에 관여하는 alkaline phosphatase의 활성도에 미치는 영향을 관찰하여 아직 확실히 밝혀져 있지 않은 치주인대조직에 대한 $1,25-(OH)_2D_3$의 생물학적 기능을 알아보고자 교정 치료 목적으로 발거된 치아로부터 치주인대세포를 배양하였다. $1,25-(OH)_2D_3$를 첨가하여 24시간 후 [${^3}H$]thymidine으로 DNA를 표지하여 세포의 증식을 관찰하였으며 $1,25-(OH)_2D_3$가 치주인대세포에서 조골세포의 표지효소인 alkaline phosphatase의 활성도에 미치는 영향을 24시간 또는 6일간 $1,25-(OH)_2D_3$ 처리후 측정한 결과 100nM농도의 $1,25-(OH)_2D_3$은 치주인대세포의 증식을 유의하게 증가시켰으며 10nM에서는 차이를 보이지 않았다. $1,25-(OH)_2D_3$을 24시간 첨가시 10nM에서는 ALP활성도는 $80.8\pm31.4$nmol로 서 대조군 $38.5\pm5.3$nmol에 비해 유의하게 증가하였으며 또한 $1,25-(OH)_2D_3$을 6일동안 첨가하였을때에도 10nM에서 $106.7\pm23.0$nmol로 대조군 $29.3\pm1.0$nmol에 비해 유의하게 증가되었다. 이상의 결과를 종합하면 $1,25-(OH)_2D_3$이 치주인대세포의 증식 및 세포기능을 시사하는 결과로 사료된다.

• 한국식품영양과학회지
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• 제24권1호
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• pp.1-9
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• 1995

1, 25(OH)2-23ene-D3 is a novel vitamine D3 analog which has a double bond between C-23 and C-24. We describe the effects of this analog on cell differentiation and cell proliferation in vitro using the human histiocytic lymphoma cell line U937, and on calcium metabolism in rats in vivo. In the present investigation 1, 25(OH)2-23ene-D3 was compared to the natural metabolite of vitamin D3, 1$\alpha$, 25-dihydroxycholecalciferol[1, 25(OH)2-23ene-D3 was more potent than 1, 25(OH)2-23ene-D3 for inhibition of proliferation and induction of differentiation of U937 cells. Especially, its effect on induction of differentiation, as measured by superoxide production and nonspecific esterase(NSE) activity, was about 20-fold more potent that 1, 25(OH)2-23ene-D3. This analog morphologically and functionally differentiated U937 cells to monocyte-macrophage phenotype showing a decrease of N/C ratio in Giemsa staining and the increase of adherence ability to surface. Intraperitoneal administration of 1, 25(OH)2-23ene-D3 to rats showed that the compound had at least 50 times less activity than 1, 25(OH)2-23ene-D3 in causing hypercalcemia and hypercalciuria. The strong direct effects of 1, 25(OH)2-23ene-D3 on cell proliferation and cell differentiation, coupled with its decreased activity of calcium metabolism make this compound an interesting candidate for clinical studies including patients with leukemia, as well as several skin disorders, such as psoriasis.

• Molecules and Cells
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• 제38권7호
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• pp.604-609
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• 2015

The active metabolite of vitamin D such as $1{\alpha}$,25-dihydroxyvitamin ($D_3(1{\alpha},25(OH)_2D_3)$ is a well-known key regulatory factor in bone metabolism. However, little is known about the potential of vitamin D as an odontogenic inducer in human dental pulp cells (HDPCs) in vitro. The purpose of this study was to evaluate the effect of vitamin $D_3$ metabolite, $1{\alpha},25(OH)_2D_3$, on odontoblastic differentiation in HDPCs. HDPCs extracted from maxillary supernumerary incisors and third molars were directly cultured with $1{\alpha},25(OH)_2D_3$ in the absence of differentiation-inducing factors. Treatment of HDPCs with $1{\alpha},25(OH)_2D_3$ at a concentration of 10 nM or 100 nM significantly upregulated the expression of dentin sialophosphoprotein (DSPP) and dentin matrix protein1 (DMP1), the odontogenesis-related genes. Also, $1{\alpha},25(OH)_2D_3$ enhanced the alkaline phosphatase (ALP) activity and mineralization in HDPCs. In addition, $1{\alpha},25(OH)_2D_3$ induced activation of extracellular signal-regulated kinases (ERKs), whereas the ERK inhibitor U0126 ameliorated the upregulation of DSPP and DMP1 and reduced the mineralization enhanced by $1{\alpha},25(OH)_2D_3$. These results demonstrated that $1{\alpha},25(OH)_2D_3$ promoted odontoblastic differentiation of HDPCs via modulating ERK activation.

• 핵의학기술
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• 제24권1호
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• pp.33-38
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• 2020

비타민D는 체내에서 칼슘 대사를 조절하여 뼈의 건강을 유지하며, 세포의 증식 및 분화의 조절, 면역 기능 등에 관여하는 중요한 역할을 한다. 부족 시 구루병, 골다공증의 위험이 높아지고 심혈관계 질환, 당뇨병, 일부 암 등의 발병 위험이 증가하는 것으로 보고되고 있다. 특히 한국은 비타민D 부족의 인구 비율이 매우 높은 국가 중 하나이다. 따라서 비타민D 부족의 진단 및 치료를 위해 혈중 25-OH-VitD 또는 25-OH-VitD3의 정확한 측정이 요구된다. 이에 본원에서 시행하고 있는 25-OH-VitD와 25-OH-VitD3검사를 비교 평가하여 비타민D에 대한 정확한 진단 및 치료에 기여하고자 한다. 25-OH-VitD와 25-OH-VitD3의 결과를 전향적으로 측정하여 상관성, 재현성, 모집단 분포율을 구하였다. 또한 2017년 4월에서 2019년 6월까지 서울아산병원 핵의학과 혈액검사실에서 측정한 내부정도관리와 대한핵의학기술학회에서 주관하는 2018년 상반기, 하반기 외부정도관리(기관간 숙련도 평가)에 참여한 결과를 비교하였다. 그 결과 97개의 검체를 대상으로 25-OH-VitD는 25-OH-VitD3 × 0.9 + 0.3 (R >0.9)로 강력한 양의 상관관계를 보였다. 반복 측정을 통한 재현성 평가 결과 평균 diff(%) 값은 7.7%, 7.4%로 모두 우수한 성적을 나타내었다. 또한 모집단 분포를 비교한 결과 통계적으로 유의한 차이를 보이지 않았다(p>0.05). 2017년 4월에서 2019년 6월까지 서울아산병원 핵의학 혈액검사실에서 측정한 내부정도관리 결과값은 평균(CV%) 6.2%, 6.8%을 나타내었다. 2018년 상반기 외부정도관리(기관간 숙련도 평가) 수행도 평가 결과 Z 값이 25-OH-VitD는 저, 중, 고농도에 대해 -1.10, -1.00, -0.90이며 25-OH-VitD3는 0.22, 0.47, 1.10이고 하반기 수행도 평가 결과는 각각 -0.80, -0.30, -0.10과 -0.01, 1.50, 1.30으로 모두 Z ≤ 2.0의 적합한 결과를 얻었다. 방사면역 측정법에 의한 25-OH-VitD와 25-OH-VitD3 검사의 비교 평가 결과 상관성, 재현성, 모집단 분포율, 내부정도관리, 외부정도관리(기관간 숙련도 평가) 모두 우수한 성적을 보였다. 따라서 혈액 내 25-OH-VitD 또는 25-OH-VitD3로 단독 측정이 가능한 방사면역 측정법은 비타민D 부족에 대한 스크리닝 검사로 적합한 것으로 사료된다.

• Nutrition Research and Practice
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• 제18권1호
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• pp.1-18
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• 2024

BACKGROUND/OBJECTIVES: Endoplasmic reticulum (ER) stress in adipose tissue causes an inflammatory response and leads to metabolic diseases. However, the association between vitamin D and adipose ER stress remains poorly understood. In this study, we investigated whether 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) alleviates ER stress in adipocytes. MATERIALS/METHODS: 3T3-L1 cells were treated with different concentrations (i.e., 10-100 nM) of 1,25(OH)₂D₃ after or during differentiation (i.e., on day 0-7, 3-7, or 7). They were then incubated with thapsigargin (TG, 500 nM) for an additional 24 h to induce ER stress. Next, we measured the mRNA and protein levels of genes involved in unfold protein response (UPR) and adipogenesis using real-time polymerase chain reaction and western blotting and quantified the secreted protein levels of pro-inflammatory cytokines. Finally, the mRNA levels of UPR pathway genes were measured in adipocytes transfected with siRNA-targeting Vdr. RESULTS: Treatment with 1,25(OH)₂D₃ during various stages of adipocyte differentiation significantly inhibited ER stress induced by TG. In fully differentiated 3T3-L1 adipocytes, 1,25(OH)₂D₃ treatment suppressed mRNA levels of Ddit3, sXbp1, and Atf4 and decreased the secretion of monocyte chemoattractant protein-1, interleukin-6, and tumor necrosis factor-α. However, downregulation of the mRNA levels of Ddit3, sXbp1, and Atf4 following 1,25(OH)₂D₃ administration was not observed in Vdr-knockdown adipocytes. In addition, exposure of 3T3-L1 preadipocytes to 1,25(OH)₂D₃ inhibited transcription of Ddit3, sXbp1, Atf4, Bip, and Atf6 and reduced the p-alpha subunit of translation initiation factor 2 (eIF2α)/eIF2α and p-protein kinase RNA-like ER kinase (PERK)/PERK protein ratios. Furthermore, 1,25(OH)₂D₃ treatment before adipocyte differentiation reduced adipogenesis and the mRNA levels of adipogenic genes. CONCLUSIONS: Our data suggest that 1,25(OH)₂D₃ prevents TG-induced ER stress and inflammatory responses in mature adipocytes by downregulating UPR signaling via binding with Vdr. In addition, the inhibition of adipogenesis by vitamin D may contribute to the reduction of ER stress in adipocytes.

• Clinical and Experimental Pediatrics
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• 제48권6호
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• pp.665-668
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• 2005

저자들은 구루병의 가족력이 있으면서 구루병의 전형적인 임상소견과 저칼슘혈증, 알칼라인 포스파타제의 상승, 2차적인 부갑상선 기능 항진증을 보인 1례를 경험하였기에 문헌고찰과 함께 보고하는 바이다.

• The Korean Journal of Physiology and Pharmacology
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• 제14권3호
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• pp.169-176
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• 2010

The hyperosmotic stimulus is regarded as a mechanical factor for bone remodeling. However, whether the hyperosmotic stimulus affects $1{\alpha}$, 25-dihydroxyvitamin $D_3$ ($1{\alpha},25(OH)_2D_3$)-induced osteoclastogenesis is not clear. In the present study, the effect of the hyperosmotic stimulus on $1{\alpha},25(OH)_2D_3$-induced osteoclastogenesis was investigated in an osteoblast-preosteoclast co-culture system. Serial doses of sucrose were applied as a mechanical force. These hyperosmotic stimuli significantly evoked a reduced number of $1{\alpha},25(OH)_2D_3$-induced tartrate-resistant acid phosphatase-positive multinucleated cells and $1{\alpha},25(OH)_2D_3$-induced bone-resorbing pit area in a co-culture system. In osteoblastic cells, receptor activator of nuclear factor ${\kappa}B$ ligand (RANKL) and Runx2 expressions were down-regulated in response to $1{\alpha},25(OH)_2D_3$. Knockdown of Runx2 inhibited $1{\alpha},25(OH)_2D_3$-induced RANKL expression in osteoblastic cells. Finally, the hyperosmotic stimulus induced the overexpression of TonEBP in osteoblastic cells. These results suggest that hyperosmolarity leads to the down-regulation of $1{\alpha},25(OH)_2D_3$-induced osteoclastogenesis, suppressing Runx2 and RANKL expression due to the TonEBP overexpression in osteoblastic cells.

• Asian-Australasian Journal of Animal Sciences
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• 제27권5호
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• pp.674-682
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• 2014

Four experiments were conducted to investigate the effect of fat-soluble vitamin administration to sows or newborn pigs on plasma vitamin status. In Exp. 1 and 2, a total of 24 and 43 newborn pigs were allotted to control and vitamin treatments (vitamin $D_3$ with variable addition of vitamins A and E) orally or by i.m. injection. In Exp. 3, pigs from Exp. 2 were allotted to 2 treatments (${\alpha}$vitamins $D_3$ and E in drinking water) for 14 d postweaning. In Exp. 4, twenty-four gestating sows were used for 2 treatments (${\pm}injection$ of a vitamin $D_3$/A/E product 2 wk prepartum). In Exp. 1 and 2, when vitamin $D_3$ was administrated orally or by i.m. injection on d 1 of age, pigs had increased plasma 25-hydroxycholecalciferol (25-OH $D_3$) concentration 10 d after administration compared with control pigs (p<0.05). The injectable administration with vitamin $D_3$ and E was able to achieve higher plasma 25-OH $D_3$ (p<0.05) and ${\alpha}$-tocopherol (p<0.05) concentrations than oral administration. At weaning, the pigs in the injection group had higher plasma 25-OH $D_3$ concentration than those in the other groups in both studies (p<0.05). In Exp. 3, water supplementation of vitamin $D_3$ and E postweaning increased plasma 25-OH $D_3$ and ${\alpha}$-tocopherol concentrations at d 14 postweaning (p<0.01). In Exp. 4, when sows were injected with the vitamin $D_3$ product prepartum, serum 25-OH $D_3$ concentrations of sows at farrowing (p<0.01), and in their progeny at birth (p<0.01) and weaning (p<0.05) were increased. These results demonstrated that fat-soluble vitamin administration to newborn pigs increased plasma 25-OH $D_3$ concentration regardless of administration routes and ${\alpha}$-tocopherol concentration by the injectable route, and that water supplementation of vitamin $D_3$ and E to nursery pigs increased plasma 25-OH $D_3$ and ${\alpha}$-tocopherol concentrations. Additionally, injecting sows with vitamin $D_3$ prepartum increased 25-OH $D_3$ in sows and their offspring. If continued research demonstrates that the serum levels of 25-OH $D_3$ are critical in weanling pigs, a variety of means to increase those levels are available to swine producers.

• Asian-Australasian Journal of Animal Sciences
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• 제29권8호
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• pp.1145-1151
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• 2016

This study was conducted to evaluate the relative bioavailability (RBV) of 25-hydroxycholecalciferol (25-OH-$D_3$) to cholecalciferol (vitamin $D_3$) in 1- to 21-d-old broiler chickens fed with calcium (Ca)- and phosphorus (P)-deficient diets. On the day of hatch, 450 female Ross 308 broiler chickens were assigned to nine treatments, with five replicates of ten birds each. The basal diet contained 0.50% Ca and 0.25% non-phytate phosphorus (NPP) and was not supplemented with vitamin D. Vitamin $D_3$ was fed at 0, 2.5, 5.0, 10.0, and $20.0{\mu}g/kg$, and 25-OH-$D_3$ was fed at 1.25, 2.5, 5.0, and $10.0{\mu}g/kg$. The RBV of 25-OH-$D_3$ was determined using vitamin $D_3$ as the standard source by the slope ratio method. Vitamin $D_3$ and 25-OH-$D_3$ intake was used as the independent variable for regression analysis. The linear relationships between the level of vitamin $D_3$ or 25-OH-$D_3$ and body weight gain (BWG) and the weight, length, ash weight, and the percentage of ash, Ca, and P in femur, tibia, and metatarsus of broiler chickens were observed. Using BWG as the criterion, the RBV value of 25-OH-$D_3$ to vitamin $D_3$ was 1.85. Using the mineralization of the femur, tibia, and metatarsus as criteria, the RBV of 25-OH-$D_3$ to vitamin $D_3$ ranged from 1.82 to 2.45, 1.86 to 2.52, and 1.65 to 2.05, respectively. These data indicate that 25-OH-$D_3$ is approximately 2.03 times as active as vitamin $D_3$ in promoting growth performance and bone mineralization in broiler chicken diets.